JPH05285374A - Microcapsules using recycled natural keratin as wall material and method for producing the same - Google Patents
Microcapsules using recycled natural keratin as wall material and method for producing the sameInfo
- Publication number
- JPH05285374A JPH05285374A JP4116819A JP11681992A JPH05285374A JP H05285374 A JPH05285374 A JP H05285374A JP 4116819 A JP4116819 A JP 4116819A JP 11681992 A JP11681992 A JP 11681992A JP H05285374 A JPH05285374 A JP H05285374A
- Authority
- JP
- Japan
- Prior art keywords
- keratin
- water
- microcapsules
- wall material
- soluble
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000003100 immobilizing effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 229940111202 pepsin Drugs 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 229920002432 poly(vinyl methyl ether) polymer Polymers 0.000 description 1
- 229920001447 polyvinyl benzene Polymers 0.000 description 1
- JLKDVMWYMMLWTI-UHFFFAOYSA-M potassium iodate Chemical compound [K+].[O-]I(=O)=O JLKDVMWYMMLWTI-UHFFFAOYSA-M 0.000 description 1
- 239000001230 potassium iodate Substances 0.000 description 1
- 235000006666 potassium iodate Nutrition 0.000 description 1
- 229940093930 potassium iodate Drugs 0.000 description 1
- HYTYHTSMCRDHIM-UHFFFAOYSA-M potassium;2-sulfanylacetate Chemical compound [K+].[O-]C(=O)CS HYTYHTSMCRDHIM-UHFFFAOYSA-M 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 238000010405 reoxidation reaction Methods 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- CLURAKRVQIPBCC-UHFFFAOYSA-M sodium;perbromate Chemical compound [Na+].[O-]Br(=O)(=O)=O CLURAKRVQIPBCC-UHFFFAOYSA-M 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- KCTAHLRCZMOTKM-UHFFFAOYSA-N tripropylphosphane Chemical compound CCCP(CCC)CCC KCTAHLRCZMOTKM-UHFFFAOYSA-N 0.000 description 1
- 238000002525 ultrasonication Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Manufacturing Of Micro-Capsules (AREA)
- Compositions Of Macromolecular Compounds (AREA)
Abstract
(57)【要約】
【目的】 本発明は、ペプチド結合切断による短鎖化処
理その他の非可逆的化学修飾を伴わないケラチンを壁材
として含む、均一性、安定性及び生体適合性等に優れ且
つ含包量が大きい再生天然ケラチンを壁材とするマイク
ロカプセル及びその製造方法の提供を目的とする。
【構成】 ケラチン含有物質を液体媒体中にて還元剤に
より処理してケラチンを抽出し該抽出液より前記還元剤
を除去することにより得られる水溶性ケラチンを壁材と
して不溶化してなるマイクロカプセル及び、前記水溶性
ケラチンの水溶液を水に不溶性又は難溶性の有機溶媒と
混合しこれを超音波処理及び／又は激しく攪拌すること
を特徴とする、再生天然ケラチンを壁材とするマイクロ
カプセルの製造方法。(57) [Summary] [Objective] The present invention contains keratin as a wall material without short-chain treatment by peptide bond cleavage or other irreversible chemical modification, and is excellent in uniformity, stability and biocompatibility. Moreover, it is an object of the present invention to provide a microcapsule having a wall material of regenerated natural keratin having a large encapsulation amount and a method for producing the same. A microcapsule obtained by treating a keratin-containing substance with a reducing agent in a liquid medium to extract keratin and removing the reducing agent from the extract to insolubilize water-soluble keratin as a wall material, and A method for producing microcapsules having regenerated natural keratin as a wall material, which comprises mixing the aqueous solution of the water-soluble keratin with an organic solvent that is insoluble or sparingly soluble in water and ultrasonically treating and / or vigorously stirring the mixture. ..
Description
【０００１】[0001]
【産業上の利用分野】本発明は、再生天然ケラチンを壁
材として含有する、染料、香料、医薬品、農薬、酵素そ
の他の薬剤の包含に又は酵素等の固定化に好適なマイク
ロカプセル及びその製造方法に関する。本明細書におい
て「再生天然ケラチン」とは、天然のケラチンに対して
酵素等によるペプチド結合の加水分解処理を加えること
なく、かつその他の非可逆的化学処理をも加えることな
く、ジスルフィド結合を還元してチオール基としてケラ
チンを一旦可溶化した後、再度チオール基同士をジスル
フィド結合させることにより再度不溶化してなる、再生
した高分子をいう。FIELD OF THE INVENTION The present invention relates to a microcapsule containing regenerated natural keratin as a wall material, which is suitable for inclusion of dyes, fragrances, pharmaceuticals, agricultural chemicals, enzymes and other drugs, or for immobilizing enzymes and the like, and the production thereof. Regarding the method. The term "regenerated natural keratin" as used herein means to reduce a disulfide bond without adding hydrolysis treatment of a peptide bond by an enzyme or the like to natural keratin and without adding any other irreversible chemical treatment. Then, it is a regenerated polymer obtained by once solubilizing keratin as a thiol group and then insolubilizing it again by disulfide-bonding thiol groups together.
【０００２】[0002]
【従来の技術】従来、医薬品等を含包させて安定性や放
出特性その他の種々の性質を改善する等の目的でマイク
ロカプセルが開発されている。2. Description of the Related Art Conventionally, microcapsules have been developed for the purpose of encapsulating pharmaceuticals and the like to improve stability, release characteristics and various other properties.
【０００３】マイクロカプの壁材として使用される材料
物質には、簡単な装置と方法によりマイクロカプセルを
製造できる等取扱が容易であることや、得られるマイク
ロカプセルがカプセル自体の量に対する薬剤等の包含量
が大きいものであることが求められる。更に医薬品や農
薬等に使用するマイクロカプセルにおいては特に、生体
適合性に優れること、取り分け毒性上問題となる架橋剤
を使用せずに製造できるものであること、生分解性を有
すること等の特徴が求められる。このためには、医薬品
等に使用し得るマイクロカプセルの壁材原料としては生
体物質を天然の又はこれに極めて近い状態で用いること
が好ましい。The material used as the wall material of the microcaps is easy to handle, such as the fact that microcapsules can be manufactured by a simple device and method, and the obtained microcapsules are such as drugs for the amount of the capsules themselves. It is required that the inclusion amount is large. Further, in microcapsules used for pharmaceuticals, agricultural chemicals, etc., in particular, features such as excellent biocompatibility, being able to be manufactured without using a cross-linking agent which causes a toxicity problem, and having biodegradability. Is required. For this purpose, it is preferable to use a biological material as a raw material for the wall material of the microcapsules that can be used for medicines or the like, in a natural or extremely close state.
【０００４】また、マイクロカプセルの製造には、マイ
クロカプセル壁材原料の性質等に応じて種々の方法が知
られているが、特に医薬品等に使用し得るマイクロカプ
セルを製造するためには、壁材原料の有する生体適合性
を損なわない方法である必要があり、従ってマイクロカ
プセル壁材原料もそのような方法を適用できる原料であ
ることが要求される。Various methods are known for producing microcapsules depending on the properties of the raw material for the wall material of the microcapsules, and in particular, for producing microcapsules which can be used for pharmaceuticals, etc. The method needs to be a method that does not impair the biocompatibility of the material, and therefore the material for the microcapsule wall material is also required to be a material to which such method can be applied.
【０００５】一方、爪や毛髪、羊毛等の獣毛や羽毛中に
は構造タンパク質としてケラチンが存在するが、ケラチ
ンそのものを壁材とするマイクロカプセル化は検討され
ていない。わずかに関連技術として、ペプシン等のタン
パク質分解酵素によるペプチド鎖の加水分解処理を経た
ケラチン（以下「ケラチン加水分解物」という。）を用
いたマイクロカプセルが開示されている（特公昭５９−
３３０１７号）。しかし、該技術においては、タンパク
質分解酵素による処理で一旦分解されたペプチド鎖の修
復処理は何ら示されておらず、従って、該ケラチン加水
分解物が鎖断片間のジスルフィド結合による架橋形成に
よってポリマー化してカプセル壁を構成した後も、切断
された各ケラチン鎖は修復を受けないままであり、天然
のケラチンを再生したものではない。On the other hand, keratin exists as a structural protein in animal hair such as nails, hair, and wool, and feathers, but microencapsulation using keratin itself as a wall material has not been studied. As a slightly related technique, a microcapsule using keratin (hereinafter referred to as "keratin hydrolyzate") obtained by hydrolyzing a peptide chain with a proteolytic enzyme such as pepsin is disclosed (Japanese Patent Publication No. 59-
33017). However, the technique does not show any repair treatment of a peptide chain once decomposed by treatment with a proteolytic enzyme, and therefore, the keratin hydrolyzate is polymerized by cross-linking due to disulfide bond between chain fragments. Even after the capsule wall has been constructed by the above method, each cleaved keratin chain remains unrepaired and does not regenerate the natural keratin.
【０００６】[0006]
【発明が解決しようとする課題】かかる状況のもとで、
本発明は、ペプチド結合の切断による低分子量化処理そ
の他の非可逆的化学修飾を伴わない、再生天然ケラチン
を壁材とする、生体適合性、生分解性の点で好ましい且
つ薬剤等の含包量が大きいマイクロカプセル及びその製
造方法を提供せんとするものである。Under these circumstances,
INDUSTRIAL APPLICABILITY The present invention uses regenerated natural keratin as a wall material, which is not accompanied by a treatment for lowering the molecular weight by cleavage of peptide bonds or other irreversible chemical modifications, is preferable in terms of biocompatibility and biodegradability, and includes an agent such as drug It is intended to provide a microcapsule having a large amount and a method for producing the same.
【０００７】[0007]
【課題を解決するための手段】上記課題の達成のため、
本発明者は、ケラチン含有物質より、ペプチド結合の分
解処理を経ることなく天然のケラチンを抽出してマイク
ロカプセルを製造する方法について種々検討した。その
結果、ケラチン含有物質から、タンパク質分解酵素によ
る加水分解処理その他の非可逆的な変成を生ずる処理を
施すことなく後述の方法によりケラチンを抽出して処理
することにより、再生天然ケラチンよりなるマイクロカ
プセルを製造することに成功した。また、該方法によっ
て製造されるマイクロカプセルは、前述のケラチン加水
分解物を用いた公知のマイクロカプセルと比較して、格
段に優れた性質を有することが確認された。[Means for Solving the Problems] To achieve the above objects,
The present inventor has conducted various studies on a method for producing microcapsules by extracting natural keratin from a keratin-containing substance without undergoing a peptide bond decomposition treatment. As a result, microcapsules composed of regenerated natural keratin are obtained by extracting and treating keratin from a keratin-containing substance by the method described below without subjecting it to hydrolysis treatment with a proteolytic enzyme or other treatment that causes irreversible modification. Was successfully manufactured. Moreover, it was confirmed that the microcapsules produced by the method have remarkably excellent properties as compared with known microcapsules using the above-mentioned keratin hydrolyzate.
【０００８】以下本発明を、マイクロカプセルの壁材原
料として用いる水溶性ケラチンの製造段階〔Ｉ〕と、該
該水溶性ケラチンを用いてマイクロカプセルを製造する
段階〔ＩＩ〕とに分けて順次説明する。 〔Ｉ．加水分解処理その他の非可逆的化学修飾を伴わな
いケラチン抽出方法及び結果〕本段階は、ケラチン含有
物質を液体媒体中において還元剤と共に攪拌することに
より還元して可溶化・抽出し、得られた抽出液より不溶
物を除去し、界面活性剤の存在下に透析その他の適当な
手段で還元剤を除去することを特徴とする。Hereinafter, the present invention will be sequentially described by dividing it into a production step [I] of water-soluble keratin used as a raw material for a wall material of microcapsules and a production step [II] of producing microcapsules using the water-soluble keratin. To do. [I. Keratin extraction method and result without hydrolysis treatment or other irreversible chemical modification] This step was obtained by solubilizing / extracting a keratin-containing substance by stirring it with a reducing agent in a liquid medium and stirring. It is characterized in that the insoluble matter is removed from the extract and the reducing agent is removed by dialysis or other suitable means in the presence of a surfactant.
【０００９】上記ケラチン含有物質としては、人毛、羊
毛その他の獣毛、羽毛、ひづめ等、真正ケラチンを含有
する物質ならいずれも使用することができる。As the keratin-containing substance, any substance containing genuine keratin such as human hair, wool or other animal hair, feathers, hoofs and the like can be used.
【００１０】上記液体媒体としては、例えば、還元に対
して安定であり且つケラチン含有物質に対し親和性のあ
る溶媒を使用することができ、例えば水又はアルコール
類若しくはアミド類等やこれらの混合物が好ましく用い
られる。該液体媒体の使用量は、ケラチン含有物質を浸
漬できる量であればよいが、ケラチン含有物質の使用量
の１０乃至４０重量倍であることが処理上好ましい。As the liquid medium, for example, a solvent that is stable against reduction and has an affinity for the keratin-containing substance can be used, and for example, water, alcohols, amides or the like, or a mixture thereof can be used. It is preferably used. The amount of the liquid medium used may be such that the keratin-containing substance can be dipped therein, but it is preferably 10 to 40 times by weight the amount of the keratin-containing substance used in terms of processing.
【００１１】上記液体媒体には、必須ではないが、特に
獣毛、毛髪、角、爪、ひづめ等の可溶化しにくい材料の
還元可溶化の効率を高める目的で所望により尿素、チオ
尿素等の水素結合切断剤、メタノール、エタノール、プ
ロパノール等のアルコール類、塩化亜鉛、ヨウ化ナトリ
ウム、臭化リチウム等の無機塩類、アンモニア、水酸化
ナトリウム等を溶解補助剤として加えることもできる。
これら溶解補助剤の添加量は適宜であるが、例えば尿素
の場合、ケラチン含有物質に対して通常３乃至１５重量
倍、好ましくは５乃至１２重量倍である。Although not essential in the above liquid medium, urea, thiourea, etc. may be optionally added for the purpose of increasing the efficiency of reductive solubilization of materials that are difficult to solubilize, such as animal hair, hair, horns, nails and hoofs. The hydrogen bond cleaving agent, alcohols such as methanol, ethanol and propanol, inorganic salts such as zinc chloride, sodium iodide and lithium bromide, ammonia, sodium hydroxide and the like can be added as a solubilizing agent.
The amount of these solubilizing agents added is appropriate, but in the case of urea, for example, it is generally 3 to 15 times by weight, preferably 5 to 12 times by weight, of the keratin-containing substance.
【００１２】上記還元にはケラチン含有物質中に存在す
るケラチンのジスルフィド結合をチオール基に還元し得
る還元剤なら一般に用いることができるが、例えばメル
カプトエタノール、チオグリコール酸、トルエン−ω−
チオール、ジチオスレイトール、ジチオエリスリトール
等のチオール系誘導体、トリフェニルホスフィン、トリ
プロピルホスフィン、トリブチルホスフィン等のリン含
有化合物、亜硫酸水素ナトリウム等の無機還元性化合物
などが好ましく用いられる。還元剤の使用量は、ケラチ
ン含有物質１０ｇに対して０．０１乃至０．５０モルと
するのが好ましく、０．０５乃至０．２５モルとするの
が更に好ましい。For the above reduction, any reducing agent capable of reducing the disulfide bond of keratin present in the keratin-containing substance to a thiol group can be generally used. For example, mercaptoethanol, thioglycolic acid, toluene-ω-
Thiol, dithiothreitol, dithioerythritol and other thiol derivatives, phosphorus-containing compounds such as triphenylphosphine, tripropylphosphine and tributylphosphine, inorganic reducing compounds such as sodium bisulfite and the like are preferably used. The amount of the reducing agent used is preferably 0.01 to 0.50 mol, and more preferably 0.05 to 0.25 mol, based on 10 g of the keratin-containing substance.
【００１３】還元可溶化は、反応を促進するためにはア
ルカリ性側で行うのが好ましいが、その場合は通常ｐＨ
１０乃至１１の範囲とするのが特に好ましい。反応は所
望により加熱して行う。反応温度、反応時間はケラチン
含有物質の可溶化の難易に応じて適宜設定することがで
きるが、例えば室温乃至１００℃にて１乃至２４時間攪
拌することができる。The reductive solubilization is preferably carried out on the alkaline side in order to accelerate the reaction.
The range of 10 to 11 is particularly preferable. The reaction is carried out by heating if desired. The reaction temperature and the reaction time can be appropriately set depending on the difficulty of solubilizing the keratin-containing substance, and for example, stirring can be performed at room temperature to 100 ° C. for 1 to 24 hours.
【００１４】還元剤の除去の操作中に液体媒体中に存在
させる必要のある前記界面活性剤は、通常、ケラチン含
有物質を還元可溶化して得た溶液とした後であって、遠
心分離、濾過等により不溶物を除去して透析工程を開始
するまでの間に該溶液に加える。該界面活性剤として
は、例えば、（１）アニオン性界面活性剤として、ドデ
シル硫酸ナトリウム等のアルキル硫酸塩、アルキル硫酸
エステル塩又は、ポリオキシエチレンアルキルエーテル
硫酸塩等の硫酸エステル塩、脂肪酸アルコールリン酸エ
ステル塩、スルホコハク酸エステル塩又はナフタレンス
ルホン酸のホルマリン縮合物等、（２）両性界面活性剤
として、ベタイン系界面活性剤等、（３）非イオン性界
面活性剤として、ポリオキシエチレンアルキルエーテル
型、脂肪酸エステル型、ポリエチレンイミン型、ポリグ
リセリンエーテル型、エステル型等、（４）カチオン性
界面活性剤として４級アンモニウム塩を使用することが
できる。これらのうち、特にアニオン性界面活性剤が好
ましい。界面活性剤の添加により、続く透析等による還
元剤除去に際し濁りや沈澱の生ずることが防止され、脱
塩精製されたケラチン溶液を得ることが可能となる。The above-mentioned surfactant, which needs to be present in the liquid medium during the operation of removing the reducing agent, is usually a solution obtained by reductively solubilizing a keratin-containing substance, and then subjected to centrifugation, Insoluble matter is removed by filtration or the like and added to the solution until the dialysis step is started. Examples of the surfactant include (1) anionic surfactants such as alkylsulfates such as sodium dodecylsulfate, alkylsulfates, sulfates such as polyoxyethylene alkyl ether sulfates, and fatty acid alcohol phosphorus. Acid ester salt, sulfosuccinic acid ester salt or formalin condensate of naphthalene sulfonic acid, (2) amphoteric surfactant, betaine-based surfactant, etc. (3) nonionic surfactant, polyoxyethylene alkyl ether Type, fatty acid ester type, polyethyleneimine type, polyglycerin ether type, ester type and the like, quaternary ammonium salt can be used as (4) cationic surfactant. Of these, anionic surfactants are particularly preferable. The addition of the surfactant prevents turbidity and precipitation from occurring during the subsequent removal of the reducing agent by dialysis or the like, and makes it possible to obtain a desalted and purified keratin solution.
【００１５】上記界面活性剤の添加量は、ケラチン溶液
の濃度や原料としたケラチン含有物質の種類によって異
なり得るため、必ずしも限定されないが、通常例えば
０．０１乃至５重量％、好ましくは０．１乃至２重量％
である。The amount of the above-mentioned surfactant added may vary depending on the concentration of the keratin solution and the kind of the keratin-containing substance used as the raw material, and is not necessarily limited, but is usually 0.01 to 5% by weight, preferably 0.1. To 2% by weight
Is.
【００１６】還元剤の除去は、透析、電気透析、限外濾
過等の適宜の手段によって行い、過剰の界面活性剤が除
去されるまで行うことができる。透析外液は例えばイオ
ン交換水とすることができる。また透析外液に還元剤
（チオール基のジスルフィド結合への変換を防止できる
還元剤）を少量（例えば、２−メルカプトエタノールの
場合０．１乃至０．５％）加えておけば、透析中におけ
るケラチン鎖のチオール基の再酸化によるケラチン鎖の
再結合を防止することができる。従って、透析中に酸素
その他の酸化剤の共存が考えられる場合には、還元剤を
少量添加することが通常好ましい。The removal of the reducing agent can be carried out by an appropriate means such as dialysis, electrodialysis, ultrafiltration or the like until the excess surfactant is removed. The dialysis external solution can be, for example, ion-exchanged water. If a small amount of reducing agent (a reducing agent capable of preventing the conversion of a thiol group into a disulfide bond) is added to the external dialysate (for example, in the case of 2-mercaptoethanol, 0.1 to 0.5%), it can be used during dialysis. It is possible to prevent recombination of the keratin chain due to reoxidation of the thiol group of the keratin chain. Therefore, it is usually preferable to add a small amount of the reducing agent when oxygen and other oxidizing agents may coexist during dialysis.
【００１７】脱塩精製して得られたケラチン水溶液はそ
のまま、又は限外濾過等により適宜濃度を調整して、或
いは使用時まで凍結乾燥その他により一旦乾燥品として
保存した後に再度水に溶解して、続くマイクロカプセル
化の段階において使用することができる。該水溶性ケラ
チンは凍結乾燥その他により乾燥させた後も水溶性であ
り、アミノ酸１００残基当たりシステイン１乃至５個、
シスチン０．５乃至３個を含み、平均分子量３００００
乃至７００００である。The keratin aqueous solution obtained by desalting and refining is dissolved in water as it is, or after adjusting the concentration as appropriate by ultrafiltration or the like, or by temporarily storing it as a dried product by freeze-drying or the like until use. , Can be used in subsequent microencapsulation steps. The water-soluble keratin is water-soluble even after being dried by freeze-drying or the like, and contains 1 to 5 cysteines per 100 amino acid residues,
Includes 0.5 to 3 cystines, average molecular weight 30,000
To 70,000.
【００１８】また、上記において使用する界面活性剤
は、還元可溶化の後で添加する代わりに還元可溶化に際
して添加しておけば、還元可溶化を促進して収率及び抽
出速度の双方を高めることが見出された。従って、還元
可溶化を一層効率よく行うためには、界面活性剤の存在
下において還元可溶化を行うことがより好ましい。ま
た、これに用いる界面活性剤としては、ドデシル硫酸ナ
トリウム等の陰イオン性界面活性剤が特に好ましい。か
かる方法によれば、典型的には、還元可溶化の後で界面
活性剤を加える場合に比べて収率は約１０乃至２０％増
大し、抽出速度は約２０乃至７０％増大する。If the surfactant used in the above is added during the reductive solubilization instead of after the reductive solubilization, the reductive solubilization is promoted and both the yield and the extraction rate are increased. It was found. Therefore, in order to carry out reductive solubilization more efficiently, it is more preferable to carry out reductive solubilization in the presence of a surfactant. Further, as the surfactant used for this, an anionic surfactant such as sodium dodecyl sulfate is particularly preferable. Such methods typically increase yields by about 10 to 20% and extraction rates by about 20 to 70% compared to adding surfactant after reductive solubilization.
【００１９】この場合、液体媒体としては、上述のもの
のうち、例えば水性溶媒、例えば水又は水とメタノー
ル、エタノール等の水混和性の有機溶媒との混合物を使
用するのが特に好ましい。また、界面活性剤存在下での
還元可溶化では、反応は十分に促進されているため、通
常、反応液のｐＨをアルカリ性側に特に調整することな
く還元可溶化を行う。その他反応条件は界面活性剤を還
元可溶化の後に加える場合と同様でよい。In this case, as the liquid medium, of the above-mentioned ones, it is particularly preferable to use, for example, an aqueous solvent, for example, water or a mixture of water and a water-miscible organic solvent such as methanol or ethanol. Further, in the reductive solubilization in the presence of a surfactant, the reaction is sufficiently promoted, and therefore the reductive solubilization is usually performed without particularly adjusting the pH of the reaction solution to the alkaline side. Other reaction conditions may be the same as in the case of adding the surfactant after the reduction and solubilization.
【００２０】界面活性剤の存在下に還元可溶化して得ら
れる水溶性ケラチンについても分析を行い、アミノ酸分
析でアミノ酸１００残基当たりシステインを通常４〜１
０個、シスチンを通常０．５〜２個を有すること、及
び、電気泳動分析で分子量１５０００〜１３００００の
タンパク質を主成分とすることが確認された。The water-soluble keratin obtained by reductive solubilization in the presence of a surfactant is also analyzed, and cysteine is usually 4 to 1 per 100 amino acid residues in the amino acid analysis.
It was confirmed that the protein has 0, usually 0.5 to 2 cystine, and that it has a protein having a molecular weight of 15,000 to 130,000 as a main component by electrophoretic analysis.
【００２１】なお、還元可溶化反応は超音波照射の下に
行うこともできる。超音波照射は、界面活性剤存在下で
の還元可溶化反応において高められたケラチン収率をも
更に高め（例えば、牛角で４５％から５５％へと高
め）、且つ、同等以上の収率を得るために要する反応時
間を短縮する（例えば牛角で２４時間から８時間へと短
縮する）効果を有する。従って、還元可溶化に際し、超
音波照射下に行うことが更に有利である。超音波照射は
適宜の超音波照射装置を用いて行うことができ、出力は
適宜設定できるが、反応液１Ｌに対して例えば５０乃至
２００Ｗとすることができる。The reduction solubilization reaction can also be carried out under ultrasonic irradiation. The ultrasonic irradiation further enhances the keratin yield enhanced in the reductive solubilization reaction in the presence of a surfactant (for example, from 45% to 55% in beef horn), and the equivalent or higher yield. It has the effect of shortening the reaction time required for obtaining (for example, shortening the beef horn from 24 hours to 8 hours). Therefore, it is more advantageous to carry out the reduction solubilization under ultrasonic irradiation. The ultrasonic wave irradiation can be performed using an appropriate ultrasonic wave irradiation device, and the output can be set appropriately, but can be set to, for example, 50 to 200 W for 1 L of the reaction liquid.
【００２２】以下に、水溶性ケラチンの製造例を記す。 〔水溶性ケラチン製造例１〕羊毛（化炭ノイル）２０ｇ
を０．８Ｍチオグリコール酸カリウム水溶液（ｐＨ１
０．５）３００ｍＬに浸漬し、５℃で３６時間攪拌を行
った。反応物から不溶物を濾過により除去し、イオン交
換水で６００ｍＬに希釈した。この液にドデシル硫酸ナ
トリウム（ＳＤＳ）１０ｇを加えて溶解し、セロファン
チューブに入れてイオン交換水（１０Ｌ）に対して２回
透析し、無色透明のケラチン水溶液（６５０ｍＬ）を得
た。The production examples of water-soluble keratin will be described below. [Water-soluble keratin production example 1] Wool (charcoal noil) 20 g
0.8 M potassium thioglycolate aqueous solution (pH 1
0.5) It was immersed in 300 mL and stirred at 5 ° C. for 36 hours. The insoluble material was removed from the reaction product by filtration, and the mixture was diluted with ion-exchanged water to 600 mL. To this solution, 10 g of sodium dodecyl sulfate (SDS) was added and dissolved, put in a cellophane tube and dialyzed twice against ion-exchanged water (10 L) to obtain a colorless and transparent keratin aqueous solution (650 mL).
【００２３】Lowry 法によりこの溶液のタンパク質定量
を行ったところ、ケラチン濃度は１．２％であった。ま
た、該水溶液を凍結乾燥して得たケラチン粉末のアミノ
酸分析を行ったところ、アミノ酸１００残基当たりシス
テインが３．３個、シスチンが１．２個であった。ま
た、ポリアクリルアミド−ＳＤＳ電気泳動法によれば、
分子量３００００乃至７００００のタンパク質が主成分
であった。When the protein of this solution was quantified by the Lowry method, the keratin concentration was 1.2%. In addition, amino acid analysis of keratin powder obtained by freeze-drying the aqueous solution revealed that 3.3 cysteines and 1.2 cystines were present per 100 amino acid residues. According to the polyacrylamide-SDS electrophoresis method,
A protein having a molecular weight of 30,000 to 70,000 was the main component.
【００２４】〔水溶性ケラチン製造例２〕脱脂羊毛（メ
リノ種）１０ｇ、ドデシル硫酸ナトリウム６．０ｇ、亜
硫酸水素ナトリウム１６ｇ及び８モル濃度の尿素３００
ｍＬの混合液を密栓のうえ、５０乃至５５℃にて１時
間、浴槽型超音波装置にて処理した。不溶物を濾過して
除去し、濾液をセロファンチューブに入れ、外液として
０．２重量％亜硫酸水素ナトリウム水溶液（３Ｌ）を用
いて透析した。透析物より少量の不溶物を遠心により除
いて得られた無色透明の水溶液約３３０ｍＬはケラチン
を１．４重量％含有していた（Lowry 法によるタンパク
質分析による）。またこのケラチンはアミノ酸分析によ
り、アミノ酸１００残基当たりシステイン７．６個、シ
スチン０．８個を有しており、ポリアクリルアミド−Ｓ
ＤＳ電気泳動によれば、分子量約４００００及び６００
００のタンパク質（それぞれ３乃至４割、５乃至６割）
を主成分としていた。[Water-soluble keratin production example 2] 10 g of defatted wool (merino seeds), 6.0 g of sodium dodecyl sulfate, 16 g of sodium bisulfite, and 300 moles of urea 300
The mixed solution of mL was sealed and treated with a bath-type ultrasonic device at 50 to 55 ° C. for 1 hour. The insoluble matter was removed by filtration, the filtrate was placed in a cellophane tube, and dialyzed using a 0.2 wt% sodium hydrogen sulfite aqueous solution (3 L) as an external solution. About 330 mL of a colorless transparent aqueous solution obtained by removing a small amount of insoluble matter from the dialyzed product by centrifugation contained 1.4% by weight of keratin (by protein analysis by the Lowry method). In addition, this keratin had 7.6 cysteines and 0.8 cystines per 100 amino acid residues, as determined by amino acid analysis.
According to DS electrophoresis, the molecular weight is about 40,000 and 600.
00 protein (30 to 40%, 50 to 60% respectively)
Was the main component.
【００２５】〔ＩＩ．本発明におけるマイクロカプセル
の製造方法及び得られるマイクロカプセルの特徴〕上記
で得られる水溶性ケラチンを用いて再生天然ケラチンを
壁材とするマイクロカプセルを製造する方法、及びそれ
によって得られるマイクロカプセルの特徴を以下に説明
する。上記で得られるケラチン水溶液をそのままで、又
は限外濾過等により濃度を適宜調整し、或いは凍結乾燥
等により一旦乾燥させたものを再度水溶液として、以下
の工程で使用することができる。[II. Method for producing microcapsule in the present invention and characteristics of microcapsule obtained] Method for producing microcapsule having regenerated natural keratin as wall material using the water-soluble keratin obtained above, and characteristics of microcapsule obtained thereby Will be described below. The aqueous solution of keratin obtained above can be used as it is in the following steps, as it is, or after the concentration is appropriately adjusted by ultrafiltration or the like, or once dried by freeze-drying or the like, as an aqueous solution again.
【００２６】なお、上記で得られた水溶性ケラチンは、
タンパク質分解酵素等によるペプチド鎖切断処理を経て
いないため、ケラチン加水分解物に比して膜の形成能が
著しく高く（試験例１を参照）、マイクロカプセルの効
率的な製造には格段に有利である。しかも、上記で得ら
れる水溶性ケラチンより製造されるマイクロカプセル
は、ケラチン加水分解物から製造されるマイクロカプセ
ルに比して格段に優れた安定性を有する（比較例１を参
照）。The water-soluble keratin obtained above is
Since it does not undergo peptide chain cleavage treatment with a proteolytic enzyme or the like, it has a significantly higher membrane-forming ability than keratin hydrolyzate (see Test Example 1), which is significantly advantageous for efficient production of microcapsules. is there. Moreover, the microcapsules produced from the water-soluble keratin obtained above have remarkably excellent stability as compared with the microcapsules produced from the keratin hydrolyzate (see Comparative Example 1).
【００２７】また、上記で得られた水溶性ケラチンより
マイクロカプセルを製造するためには、例えば、相分離
法、噴霧凝固造粒法その他マイクロカプセルの製造方法
として知られている種々の方法のいずれを用いることも
でき、いずれの方法でも、安定で生体適合性の点で好ま
しいマイクロカプセルが容易に製造できる。なお、とり
わけ微細かつ均一な粒径を有しカプセル壁が極めて薄く
且つ安定性が高い、という特段の特徴を備えたマイクロ
カプセルの製造を目的とする場合には、後述の超音波法
が、極めて簡便にこの目的の達成を可能にするから、特
に好ましい。In order to produce microcapsules from the water-soluble keratin obtained above, for example, any of various methods known as a method for producing microcapsules, such as a phase separation method, a spray coagulation granulation method and the like. Can be used, and by any method, microcapsules preferable in terms of stability and biocompatibility can be easily produced. Incidentally, in particular, for the purpose of producing a microcapsule having a particular feature that the capsule wall has a fine and uniform particle size and is extremely thin and highly stable, the ultrasonic method described below is extremely It is particularly preferable because it makes it possible to easily achieve this object.
【００２８】〔１．好ましい各方法の概要〕以下（１）
乃至（４）に本発明のマイクロカプセルの各種製造方法
のうち、好ましい主要なものの概要を示す。[1. Outline of Preferred Methods] Below (1)
Out of various methods for producing microcapsules of the present invention, preferable main ones are outlined in (4).
【００２９】（１）超音波照射法： ケラチン水溶液
と、水に不溶性又は難溶性の有機溶媒等（例えばトルエ
ン、ヘキサン等の有機溶媒又は油状の薬物等）との混合
物（ケラチン水溶液／有機溶媒等の体積比は当該マイク
ロカプセルの製造目的に応じて変化するが、通常０．１
乃至１０）を、例えば０℃乃至５０℃の温度範囲にて、
例えば１０秒乃至１０分間超音波照射する。ケラチンの
アミノ酸残基のうちシステイン残基が有するメルカプト
基がジスルフィド結合へと変化することによってケラチ
ン鎖間に架橋形成がなされる結果、水溶性のケラチンが
水に不溶の再生天然ケラチンとなって前記溶媒等の微細
な粒子表面上に極めて薄い安定な皮膜を形成し、当該溶
媒等を芯物質として効率的に閉じ込めてなる均一な粒径
のマイクロカプセルが得られる（実施例３及び４を参
照）。(1) Ultrasonic irradiation method: A mixture of a keratin aqueous solution and a water-insoluble or sparingly soluble organic solvent (eg, an organic solvent such as toluene or hexane or an oily drug) (keratin aqueous solution / organic solvent, etc.) The volume ratio of V varies depending on the production purpose of the microcapsules, but is usually 0.1.
To 10) in a temperature range of 0 ° C to 50 ° C, for example,
For example, ultrasonic irradiation is performed for 10 seconds to 10 minutes. Among the amino acid residues of keratin, a mercapto group of a cysteine residue is converted into a disulfide bond to form a crosslink between keratin chains, and as a result, a water-soluble keratin becomes a water-insoluble regenerated natural keratin. A very thin and stable film is formed on the surface of fine particles such as a solvent, and microcapsules having a uniform particle size can be obtained in which the solvent or the like is efficiently confined as a core substance (see Examples 3 and 4). ..
【００３０】（２）振動・攪拌法： 上記（１）の混合
物（ケラチン水溶液及び溶媒の）に過酸化水素、過ヨウ
素酸ナトリウムなどＳＨ基を酸化してジスルフィド結合
に変換することのできる酸化剤を加えた後、ボルテック
スミキサーや攪拌モーターなどで激しく振動・攪拌す
る。超音波法と同様な簡便な操作で、再生天然ケラチン
を壁材とするマイクロカプセルが製造できる（実施例５
を参照）。(2) Vibration / stirring method: An oxidizing agent capable of oxidizing the SH group such as hydrogen peroxide or sodium periodate into the mixture (of the keratin aqueous solution and the solvent) of the above (1) to convert it into a disulfide bond. After adding, vigorously shake and stir with a vortex mixer or stirring motor. Microcapsules containing regenerated natural keratin as a wall material can be produced by a simple operation similar to the ultrasonic method (Example 5).
See).
【００３１】（３）上記二方法の変法： 上記（１）の
混合物を、窒素ガスなど酸化能力を欠くガス雰囲気下に
て、超音波照射装置、ボルテックスミキサーや攪拌モー
ターなどで激しく振動・攪拌して乳濁液とした上で、上
記（２）で述べた酸化剤を加えて攪拌する方法（実施例
６を参照）。(3) Modified method of the above two methods: The mixture of (1) above is vigorously agitated and stirred by an ultrasonic irradiation device, a vortex mixer, a stirring motor, etc. in a gas atmosphere such as nitrogen gas lacking an oxidizing ability. And an emulsion, and then the oxidizer described in (2) above is added and stirred (see Example 6).
【００３２】（４）他の壁材成分を加えた方法： ケラ
チン水溶液と他のタンパク質水溶液の混合物、又はケラ
チン水溶液と非タンパク質でＳＨ基もしくはジスルフィ
ド結合を持つ化合物の水溶液との混合物を壁材原料とし
て用い、上記（１）乃至（３）に記載の方法で処理して
再生天然ケラチンを壁材として含むマイクロカプセルを
製造する（実施例７及び８）。混合する他成分に応じ
て、得られるマイクロカプセルの性質を変化させること
が可能となる。(4) Method in which other wall material component is added: A mixture of keratin aqueous solution and other protein aqueous solution or a mixture of keratin aqueous solution and non-protein aqueous solution of compound having SH group or disulfide bond is used as wall material. The microcapsules containing the regenerated natural keratin as a wall material are produced by treating the microcapsules by the method described in (1) to (3) above (Examples 7 and 8). The properties of the resulting microcapsules can be changed depending on the other components to be mixed.
【００３３】上記（１）乃至（４）において、あらかじ
め有機溶媒等に染料、香料、医薬品などの物質を溶かし
たものを使用すれば、これらは芯物質として効率よくマ
イクロカプセル内に含包される（実施例８及び９）。In the above (1) to (4), when a substance such as a dye, a fragrance, or a drug is dissolved in an organic solvent in advance, these are efficiently contained in the microcapsule as a core substance. (Examples 8 and 9).
【００３４】〔２．公知成分〕以下に本発明のマイクロ
カプセルの製造に用いる公知成分について詳細に説明す
る。 （ｉ）ケラチン含有水溶液： 下記のケラチン水溶液
（ｉ−ａ）単独、該ケラチン水溶液（ｉ−ａ）に以下の
（ｉ−ｂ）若しくは（ｉ−ｃ）に記載の物質を加えた混
合物、又は該ケラチン水溶液（ｉ−ａ）に（ｉ−ｂ）と
（ｉ−ｃ）とを加えた混合物である。[2. Known Components] The known components used for producing the microcapsules of the present invention will be described in detail below. (I) Keratin-containing aqueous solution: The following keratin aqueous solution (ia) alone, a mixture of the keratin aqueous solution (ia) to which the following (ib) or (ic) substances are added, or It is a mixture in which (ib) and (ic) are added to the keratin aqueous solution (ia).
【００３５】（ｉ−ａ）ケラチン水溶液： ケラチン原
料として羊毛、人髪、鶏羽、犬毛、牛角などケラチンを
含むものを用いて上記の方法で製造したケラチンの水溶
液である。(Ia) Keratin aqueous solution: An aqueous solution of keratin prepared by the above-mentioned method using keratin raw materials containing keratin such as wool, human hair, chicken feathers, dog hair and beef horn.
【００３６】（ｉ−ｂ）ケラチン水溶液と混合される他
のタンパク質またはペプチド：コラーゲン、ゼラチン、
フィブリノーゲン、シルク、卵白リゾチーム、インスリ
ンなどのメルカプト基やジスルフィド結合を有するタン
パク質；グリシル−グリシル−システイン（Gly-Gly-Cy
s)や（グリシル−グリシル−シスチン）2 〔(Gly-Gly-C
yt )2 〕などのペプチド。またはこれらに存在する複数
のジスルフィド結合の全部または一部が還元されてメル
カプト基となっているもの。(Ib) Other proteins or peptides mixed with the aqueous keratin solution: collagen, gelatin,
Proteins with mercapto groups and disulfide bonds such as fibrinogen, silk, egg white lysozyme, and insulin; Gly-Gly-Cy
s) and (glycyl-glycyl-cystine) 2 [(Gly-Gly-C
peptides such as yt) 2 ]. Alternatively, all or part of the plurality of disulfide bonds present in these are reduced to a mercapto group.
【００３７】（ｉ−ｃ）非タンパク質でメルカプト基ま
たはジスルフィド基を持つもの：ＳＨ基を担持せしめた
ポリビニルアルコール（例：平均分子量２０００に対し
てＳＨ基が１乃至２０個）などの高分子の水溶液、およ
びグルタチオン、２−メルカプトエタノールなど。(Ic) Non-protein having a mercapto group or a disulfide group: a polymer such as polyvinyl alcohol carrying SH groups (eg, 1 to 20 SH groups based on an average molecular weight of 2000) Aqueous solution, glutathione, 2-mercaptoethanol and the like.
【００３８】（ｉｉ）有機溶媒等：本発明に使用する有
機溶媒としては、水に難溶なトルエン、キシレン、ヘキ
サン、デカン、シクロヘキサンなどの炭化水素系溶媒が
最も好ましいが、ジエチルエーテルなどのエーテル型溶
媒やフルオロシクロヘキサン、フロン１１３などの含ハ
ロゲン炭化水素も使用できる。しかし、これらに限るも
のではなく、水に溶解性の低い溶媒であれば使用するこ
とができる。また、溶媒に限らず、水に不溶性又は難溶
性のその他の液状物質、例えばビタミンＥアセテートそ
の他の油状の薬物等も使用することができる。(Ii) Organic solvent and the like: As the organic solvent used in the present invention, hydrocarbon solvents such as toluene, xylene, hexane, decane and cyclohexane which are poorly soluble in water are most preferable, but ethers such as diethyl ether are preferable. Type solvents and halogen-containing hydrocarbons such as fluorocyclohexane and CFC 113 can also be used. However, the solvent is not limited to these, and any solvent having low solubility in water can be used. Further, not only the solvent but also other liquid substances insoluble or sparingly soluble in water, such as vitamin E acetate and other oily drugs, can be used.
【００３９】（ｉｉｉ）酸化剤：酸化剤を使用する場合
には、空気、酸素、過酸化水素、過ヨウ素酸ナトリウ
ム、過臭素酸ナトリウム、過硫酸アンモニウム、ヨウ素
酸カリウムなどの、メルカプト基をジスルフィド結合に
酸化し得るものを用いるのが好ましい。また、これら酸
化剤と共に、酸化促進剤または触媒として、例えば鉄イ
オン、を併用することもできる。(Iii) Oxidizing agent: When an oxidizing agent is used, a mercapto group such as air, oxygen, hydrogen peroxide, sodium periodate, sodium perbromate, ammonium persulfate, potassium iodate, etc. is disulfide-bonded. It is preferable to use a substance that can be oxidized. Further, for example, iron ions can be used together with these oxidizing agents as an oxidation promoter or a catalyst.
【００４０】〔３．マイクロカプセル形成の具体的方法
例〕マイクロカプセルを形成させるための方法として
は、以下の通り、既知のマイクロカプセル製造方法が種
々使用できるが、粒径が微細且つ均一でありカプセル壁
が極めて薄く且つ安定性が高いマイクロカプセルを簡便
に製造することができるという点で、超音波法が特に好
ましい。[3. Examples of specific method for forming microcapsules] As a method for forming microcapsules, various known microcapsule production methods can be used as follows, but the particle size is fine and uniform, and the capsule wall is extremely thin and The ultrasonic method is particularly preferable because microcapsules having high stability can be easily produced.
【００４１】（３−ｉ）超音波法： 超音波照射装置は
試料に超音波を照射することができる装置であればいず
れの装置でもよいが、マイクロカプセルの生成効率を高
めるには、チタンなど金属のプローブ先端より超音波を
発生させるプローブ型の装置が好ましい。超音波照射条
件は、試料の成分と体積により適宜調製するが、一般に
ケラチン含有水溶液と有機溶媒等の合計体積の１０ｍＬ
に対し、３０乃至５０Ｗにて１０秒間乃至５分間照射す
ればよい。(3-i) Ultrasonic method: The ultrasonic irradiation device may be any device as long as it can irradiate the sample with ultrasonic waves, but titanium or the like can be used to enhance the generation efficiency of the microcapsules. A probe type device that generates ultrasonic waves from a metal probe tip is preferable. The ultrasonic irradiation conditions are appropriately adjusted depending on the components and volume of the sample, but generally 10 mL of the total volume of the keratin-containing aqueous solution and the organic solvent, etc.
On the other hand, irradiation may be performed at 30 to 50 W for 10 seconds to 5 minutes.
【００４２】なお、含ハロゲン炭化水素などを有機溶媒
として用いると、マイクロカプセルの生成効率と含包効
率が低くなる場合があるが、その場合には、超音波処理
に先立って微量の過酸化水素などの酸化剤を添加してお
けば、マイクロカプセルの生成効率を増加させることが
できる。When a halogen-containing hydrocarbon or the like is used as an organic solvent, the microcapsule production efficiency and the encapsulation efficiency may be lowered. In that case, a small amount of hydrogen peroxide is added prior to the ultrasonic treatment. If an oxidizing agent such as is added, the production efficiency of microcapsules can be increased.
【００４３】また、窒素ガスなど酸化能力を欠く気体の
雰囲気下にて超音波処理し、生じた乳濁液の混合物に酸
化剤を加えてもよい。この手法は、芯物質が酸化されや
すい場合には、芯物質の酸化を防ぎつつマイクロカプセ
ル化する効果があり、特に有用である。酸化剤の使用料
はおおむね原料中のＳＨ基１個に対し１乃至６倍の酸化
剤分子の個数に相当する量である。Alternatively, an oxidizer may be added to the resulting mixture of emulsions by ultrasonication in an atmosphere of a gas such as nitrogen gas that lacks oxidizing ability. This method is particularly useful because it has an effect of microcapsulating while preventing oxidation of the core substance when the core substance is easily oxidized. The amount of the oxidizing agent used is generally an amount corresponding to 1 to 6 times the number of molecules of the oxidizing agent with respect to one SH group in the raw material.
【００４４】ケラチンとケラチン以外の壁材原料〔上記
2.の（ｉ−ｂ）及び（ｉ−ｃ）〕の混合比は、ケラチン
に対して１乃至５００重量％用いることができるが、例
えば、コラーゲンやゼラチン、フィブリノーゲンでは３
０乃至５００重量％、シルクでは１乃至１００重量％、
ＳＨ基担持ポリビニルアルコールでは１０乃至２００重
量％を用いる。有機溶媒量は、芯物質の溶解性に応じて
変わるが、ケラチンと上記壁材原料の水溶液全量に対し
て０．１乃至５倍体積、通常は０．５乃至２倍体積を使
用する。Keratin and wall material other than keratin [above
The mixing ratio of (i-b) and (i-c) in 2) can be 1 to 500% by weight with respect to keratin. For example, collagen, gelatin, and fibrinogen are 3% by weight.
0 to 500% by weight, silk 1 to 100% by weight,
In the SH group-supporting polyvinyl alcohol, 10 to 200% by weight is used. Although the amount of the organic solvent varies depending on the solubility of the core substance, it is used in an amount of 0.1 to 5 times by volume, usually 0.5 to 2 times by volume, relative to the total amount of the aqueous solution of keratin and the wall material.
【００４５】（３−ｉｉ）攪拌法： 壁材原料は超音波
法と同様であるが、超音波操作の代わりにボルテックス
ミキサーで激しく振動させつつ攪拌するか、又は攪拌モ
ーターにより激しく攪拌する。なお、処理前に酸化剤を
微量（ＳＨ基１個に対し１乃至６倍の酸化剤分子個数）
加えておくか、攪拌して生じた乳濁状の混合物に酸化剤
を加え、その後、酸化剤がよく混ざるよう緩く攪拌して
もよい。(3-ii) Stirring method: The raw material for the wall material is the same as in the ultrasonic method, but instead of ultrasonic operation, stirring is performed while vigorously vibrating with a vortex mixer, or vigorous stirring is performed with a stirring motor. Before the treatment, trace amount of oxidizer (1 to 6 times the number of oxidizer molecules per SH group)
The oxidizing agent may be added or added to the emulsion-like mixture formed by stirring, and then gently stirred so that the oxidizing agent is well mixed.
【００４６】（３−ｉｉｉ）ｐＨ調製による方法： 芯
物質たる前記有機溶媒等をケラチン水溶液中に分散さ
せ、これにクエン酸、酢酸等の酸を加えてｐＨを４乃至
５付近に調整する。これにより、水溶性ケラチンは等電
点に達して該芯物質を核にして凝集沈着しこれを包囲し
てマイクロカプセルの原型が形成される。ついで空気、
酸素その他の酸化剤を導入・添加することにより、水溶
性ケラチンの各分子のメルカプト基同士が酸化されてジ
スルフィド結合を形成し高分子化して不溶性の被膜とな
り、マイクロカプセルが形成される。(3-iii) Method by adjusting pH: The organic solvent or the like as a core substance is dispersed in an aqueous keratin solution, and an acid such as citric acid or acetic acid is added to adjust the pH to about 4 to 5. As a result, the water-soluble keratin reaches the isoelectric point, aggregates and deposits with the core substance as the nucleus, and surrounds the core substance to form a prototype of microcapsules. Then air
By introducing and adding oxygen and other oxidizing agents, the mercapto groups of each molecule of the water-soluble keratin are oxidized to form a disulfide bond and polymerize to form an insoluble film, forming microcapsules.
【００４７】（３−ｉｖ）噴霧乾燥法： 水溶性又は水
に不溶性の芯物質をケラチン水溶液中に溶解又は分散さ
せ、これをスプレードライヤーで噴霧し、熱風と接触さ
せ水分を蒸発させて乾燥させることにより、マイクロカ
プセルが形成される。該方法は、水溶性及び水不溶性の
いずれの物質をも芯物質としてマイクロカプセル化する
ことができ、カプセル壁の不溶化も容易に行われるとい
う利点を有する。(3-iv) Spray drying method: A water-soluble or water-insoluble core substance is dissolved or dispersed in an aqueous solution of keratin, and this is sprayed with a spray dryer and brought into contact with hot air to evaporate the water content and dry it. As a result, microcapsules are formed. The method has an advantage that both a water-soluble substance and a water-insoluble substance can be microencapsulated as a core substance, and insolubilization of the capsule wall can be easily performed.
【００４８】（３−ｖ）コアセルベートの形成による方
法： ｐＨ５以上に調整したケラチン水溶液中にｐＨの
いかんによらず負に荷電しているポリアニオン、例えば
アラビアゴムの水溶液を添加して希釈水溶液とし、これ
に水に難溶性又は不溶性の芯物質を分散させる。この系
に酢酸、クエン酸等の酸を添加してｐＨを低下させるこ
とにより、ケラチン分子の荷電のみを負から正に変化さ
せ、芯物質を核にして水溶性ケラチンとポリアニオンと
の複合コアセルベートの膜を形成させる。次いで適宜酸
化処理を行うことにより、この膜が水に不溶性となりマ
イクロカプセルが形成される。かかる複合コアセルベー
トを形成し得るポリアニオンの他の例としては、アルギ
ン酸ナトリウム、寒天、カルボキシメチルセルロー
ス、、ポリビニルメチルエーテル無水マレイン酸共重合
体、ポリビニルベンゼンスルホン酸、ホルマリンとナフ
タレンスルホン酸との縮合物等、分子中に酸基を有する
ポリマーや界面活性剤等が挙げられる。(3-v) Method by formation of coacervate: An aqueous solution of keratin adjusted to pH 5 or higher is added with an aqueous solution of a polyanion negatively charged regardless of pH, for example, an aqueous solution of gum arabic to prepare a diluted aqueous solution. A hardly soluble or insoluble core substance is dispersed in this. By adding an acid such as acetic acid or citric acid to this system to lower the pH, only the charge of the keratin molecule is changed from negative to positive, and the complex coacervate of water-soluble keratin and polyanion with the core substance as the nucleus is used. Form a film. Then, by appropriately performing an oxidation treatment, this film becomes insoluble in water to form microcapsules. Other examples of polyanions capable of forming such a complex coacervate, sodium alginate, agar, carboxymethyl cellulose, polyvinyl methyl ether maleic anhydride copolymer, polyvinyl benzene sulfonic acid, a condensate of formalin and naphthalene sulfonic acid, etc., Examples thereof include polymers having an acid group in the molecule and surfactants.
【００４９】また、ケラチン水溶液に芯物質を分散さ
せ、これにアルコール等又は無機塩類を添加することに
よって、芯物質を核として単純コアセルベート又はソル
トコアセルベートの膜を形成させることができ、これを
適宜酸化処理して不溶化させることによりマイクロカプ
セルが形成される。Further, by dispersing the core substance in an aqueous solution of keratin and adding alcohol or an inorganic salt to the core substance, a simple coacervate or salt coacervate film can be formed with the core substance as a nucleus, which is appropriately oxidized. The microcapsules are formed by treatment and insolubilization.
【００５０】〔４．マイクロカプセルの単離〕上記（３
−ｉ）乃至（３−ｉｉｉ）、及び（３−ｖ）で得られた
マイクロカプセルの単離は次のようにして行うのが好ま
しい。 （４−ｉ）処理液をそのまま濃縮するか乾燥（凍結乾燥
など）する。[4. Isolation of Microcapsules] (3)
The isolation of the microcapsules obtained in -i) to (3-iii) and (3-v) is preferably performed as follows. (4-i) The treatment solution is concentrated as it is or dried (freeze-drying, etc.).
【００５１】（４−ｉｉ）処理液を遠心して、マイクロ
カプセルを分離分画する。このままではマイクロカプセ
ルの外部にマイクロカプセルの生成に与からなかった壁
材原料や酸化剤などが不純物として残る場合があるた
め、また、マイクロカプセルを更に改質するため、マイ
クロカプセル画分に水や緩衝液を加えて攪拌後遠心し、
再びマイクロカプセルを分離分画する。この操作を数回
繰り返した後、マイクロカプセル分散液をそのまま利用
するか、濃縮または乾燥（凍結乾燥など）する。(4-ii) The treatment liquid is centrifuged to separate and fractionate the microcapsules. If left as it is, the wall material or oxidizing agent that was not involved in the generation of the microcapsules may remain as impurities, and in order to further modify the microcapsules, water or water may be added to the microcapsule fraction. Add a buffer solution, stir and centrifuge,
The microcapsules are separated and fractionated again. After repeating this operation several times, the microcapsule dispersion is used as it is, or concentrated or dried (freeze-drying, etc.).
【００５２】（４−ｉｉｉ）処理液を、セロファン膜な
どの半透膜を利用して水や緩衝液あるいは香料、染料、
生物活性薬物などを溶かした水溶液に対して、透析す
る。透析後の液をそのまま利用するか、濃縮または乾燥
（凍結乾燥などで）する。(4-iii) The treatment liquid is treated with a semipermeable membrane such as a cellophane membrane, water, a buffer solution, a fragrance, a dye,
Dialyze against an aqueous solution containing a bioactive drug. Use the solution after dialysis as it is, or concentrate or dry (by freeze-drying, etc.).
【００５３】以上により得られるマイクロカプセルの直
径は、ケラチン含有水溶液の種類、ケラチン含有水溶液
に対する有機溶媒の体積比、振動又は攪拌の与え方と時
間などにより変動し一概に規定できないが、例えば、
２．５重量％のケラチン水溶液とトルエンとの１：１体
積混合物（２０ｍＬ）を室温にて３分間、５０Ｗにて超
音波処理した場合は、１乃至３μｍを主とした微小球で
あることが光散乱法により求められ、同サンプルを透過
型電子顕微鏡で観察したところ、壁厚は約０．０２μｍ
の極めて薄い、紙風船様の形態であった。The diameter of the microcapsules obtained as described above varies depending on the kind of the keratin-containing aqueous solution, the volume ratio of the organic solvent to the keratin-containing aqueous solution, the method of giving vibration or stirring, and the time, but cannot be unconditionally specified.
When a 1: 1 volume mixture (20 mL) of 2.5 wt% keratin aqueous solution and toluene is sonicated at room temperature for 3 minutes at 50 W, it may be microspheres mainly having 1 to 3 μm. Obtained by the light scattering method and observing the sample with a transmission electron microscope, the wall thickness is about 0.02 μm.
It was a very thin paper balloon-like form.
【００５４】[0054]
【実施例】次に実施例を挙げて更に詳しく説明するが、
本発明はこれらに限定されるものではない。 （実施例１）ｐＨ調節によるマイクロカプセル化： 製造例１で得たケラチン水溶液（ケラチン濃度１．２重
量％）５００ｍＬ中に、ビタミンＥアセテート５ｇを均
一に分散させ、攪拌しながらこれに５％クエン酸水溶液
を滴下して加えｐＨ４にてケラチンを凝集させ、分散し
たビタミンＥアセテートの周囲にマイクロカプセルの原
型を形成させた。これを遠心分離により分離し、空気を
吹き込んで乾燥しつつ空気酸化させ、更に減圧乾燥して
マイクロカプセルを完成させた。得られたマイクロカプ
セルは、ｐＨのいかんに関わりなく２０℃の水に不溶で
あった。[Examples] Next, more detailed description will be given with reference to Examples.
The present invention is not limited to these. (Example 1) Microencapsulation by pH adjustment: In 500 mL of the keratin aqueous solution (keratin concentration 1.2% by weight) obtained in Production Example 1, 5 g of vitamin E acetate was uniformly dispersed, and 5% was added thereto while stirring. A citric acid aqueous solution was added dropwise to aggregate keratin at pH 4 to form a prototype of microcapsules around the dispersed vitamin E acetate. This was separated by centrifugation, air was blown in to dry and air-oxidized, and further dried under reduced pressure to complete microcapsules. The obtained microcapsules were insoluble in water at 20 ° C regardless of the pH.
【００５５】（実施例２）噴霧乾燥によるマイクロカプ
セル化： 製造例１で得たケラチン水溶液（ケラチン濃度１．２重
量％）５００ｍＬに、メチレンブルー２ｇを加えて分散
させ、これをスプレードライヤーで噴霧し、熱風を接触
させて水分を蒸発、乾燥させることにより、メチレンブ
ルーの周囲に水に不溶性のケラチンの被膜を形成させて
マイクロカプセル化を行った。(Example 2) Microencapsulation by spray drying: To 500 mL of the keratin aqueous solution (keratin concentration 1.2% by weight) obtained in Production Example 1 was added 2 g of methylene blue to disperse, and this was sprayed with a spray dryer. By contacting with hot air to evaporate and dry the water, a water-insoluble keratin film was formed around methylene blue to carry out microencapsulation.
【００５６】（実施例３）広口試験管に製造例１で得た
ケラチン水溶液（ケラチン濃度１．２重量％）１０ｍＬ
とトルエン１０ｍＬを加え、マグネットバーで混合物を
間接的に攪拌しつつ、２５℃にて５０Ｗの出力で３分
間、超音波照射した。生じた白色懸濁液を３０００回転
／分で１５分間遠心し、白濁固形物質を分離し、水（２
０ｍＬ）を加え、攪拌後、同様に遠心した。同じ洗浄操
作を更に２回繰り返した後凍結乾燥した。得られた白色
粉末状物質（約０．１０ｇ）は、透過型電子顕微鏡観察
によれば比較的均一なマイクロカプセルであり、壁厚約
０．０２μｍ、直径１．２乃至１．５μｍであった。白
色粉末状物質の光散乱測定によってもほぼ同様の直径分
布が示された。(Example 3) 10 mL of the keratin aqueous solution (keratin concentration 1.2% by weight) obtained in Production Example 1 was placed in a wide-mouth test tube.
And 10 mL of toluene were added thereto, and the mixture was subjected to ultrasonic irradiation at 25 ° C. with an output of 50 W for 3 minutes while indirectly stirring the mixture. The resulting white suspension was centrifuged at 3000 rpm for 15 minutes to separate a cloudy solid substance, and water (2
0 mL) was added, and the mixture was stirred and then centrifuged in the same manner. The same washing operation was repeated twice more and then freeze-dried. The obtained white powdery substance (about 0.10 g) was a relatively uniform microcapsule as observed by a transmission electron microscope, and had a wall thickness of about 0.02 μm and a diameter of 1.2 to 1.5 μm. .. Light scattering measurement of the white powdery substance showed almost the same diameter distribution.
【００５７】（比較例１）製造例１で得たケラチン水溶
液の代わりに、特公昭５９−３３０１７号記載の方法に
よるケラチン加水分解物（平均分子量２２００）を用い
た以外は実施例３と同様にしてマイクロカプセル化を試
みた。しかしながら、該水溶性ケラチン加水分解物より
得られた粒状物質は極めてもろく、その水中分散体は室
温で放置するのみで崩壊し内部のトルエンを遊離してし
まった。(Comparative Example 1) The same procedure as in Example 3 was carried out except that the keratin hydrolyzate (average molecular weight 2200) obtained by the method described in JP-B-59-33017 was used in place of the keratin aqueous solution obtained in Production Example 1. And tried microencapsulation. However, the granular substance obtained from the water-soluble keratin hydrolyzate was extremely brittle, and its aqueous dispersion disintegrated and liberated the internal toluene only by leaving it at room temperature.
【００５８】（実施例４）広口試験管に製造例２で得た
ケラチン水溶液（ケラチン濃度１．４重量％）（１０ｍ
Ｌ）とトルエン（１０ｍＬ）を入れ、マグネットバーで
混合物を間接的に攪拌しつつ、２５℃にて５０Ｗの出力
で３分間、超音波照射した。生じた白色懸濁液を３００
０回転／分で１５分間遠心し、白濁固形物質を分離し、
水（２０ｍＬ）を加え、攪拌後、同様に遠心した。同じ
洗浄操作を更に２回繰り返した後、凍結乾燥した。得ら
れた白色粉末状物質（約０．１１ｇ）は、透過型電子顕
微鏡観察によれば、比較的均一なマイクロカプセルであ
り、壁厚は約０．０２μｍ、直径は１．２乃至１．５μ
ｍである。白色粉末状物質の光散乱測定もほぼ同様の直
径分布を示した。原料のケラチン水溶液を凍結乾燥して
得たケラチン粉末のアミノ酸分析では、アミノ酸１００
残基当たりシステインが７．５個、シスチンが０．９個
であったが、マイクロカプセルではシスチン含量が約８
個に増加していた。他のアミノ酸残基は原料における値
とほぼ一致した。Example 4 A keratin aqueous solution (keratin concentration: 1.4% by weight) obtained in Production Example 2 was placed in a wide-mouth test tube (10 m
L) and toluene (10 mL) were added, and the mixture was subjected to ultrasonic irradiation at 25 ° C. and 50 W for 3 minutes while indirectly stirring the mixture. The resulting white suspension is 300
Centrifuge at 0 rpm for 15 minutes to separate the cloudy solid material,
Water (20 mL) was added, and the mixture was stirred and then centrifuged in the same manner. The same washing operation was repeated twice more and then freeze-dried. The obtained white powdery substance (about 0.11 g) is a relatively uniform microcapsule according to transmission electron microscope observation and has a wall thickness of about 0.02 μm and a diameter of 1.2 to 1.5 μm.
m. The light scattering measurement of the white powdery substance showed almost the same diameter distribution. In the amino acid analysis of keratin powder obtained by freeze-drying the raw material keratin aqueous solution, 100 amino acids were obtained.
There were 7.5 cysteines and 0.9 cystines per residue, but the cystine content was about 8 in microcapsules.
It was increasing to individual. The values of other amino acid residues were almost the same as those in the raw material.
【００５９】（実施例５）広口試験管に製造例２で得た
ケラチン水溶液（ケラチン濃度１．４重量％）（１０ｍ
Ｌ）、３０％過酸化水素水（０．０５ｍＬ）とトルエン
（１０ｍＬ）を入れ、ボルテックスミキサーで２５℃で
５分間激しく振動攪拌した。生じた白色懸濁液を２００
０回転／分で１５分間遠心し、白濁固形物質を分離し、
水（２０ｍＬ）を加え、攪拌後、同様に遠心した。同じ
洗浄操作を更に２回繰り返した後、凍結乾燥した。得ら
れた白色粉末状物質（約０．１１ｇ）の透過型電子顕微
鏡観察によれば、生じたマイクロカプセルの直径は、や
やばらつくものの、３乃至１０μｍである。Example 5 In a wide-mouth test tube, the keratin aqueous solution (keratin concentration 1.4% by weight) obtained in Production Example 2 (10 m
L), 30% aqueous hydrogen peroxide (0.05 mL) and toluene (10 mL) were added, and the mixture was vigorously shaken and stirred at 25 ° C. for 5 minutes with a vortex mixer. The resulting white suspension is 200
Centrifuge at 0 rpm for 15 minutes to separate the cloudy solid material,
Water (20 mL) was added, and the mixture was stirred and then centrifuged in the same manner. The same washing operation was repeated twice more and then freeze-dried. According to a transmission electron microscope observation of the obtained white powdery substance (about 0.11 g), the diameter of the generated microcapsules is 3 to 10 μm although it varies slightly.
【００６０】（実施例６）広口試験管に製造例２で得た
ケラチン水溶液（ケラチン濃度１．４重量％）（１０ｍ
Ｌ）とトルエン（１０ｍＬ）を入れ、窒素ガス雰囲気
下、２５℃で５分間超音波処理した。生じた白色懸濁液
に３０％過酸化水素水（０．０７ｍＬ）を加え、緩く振
盪後、１５分放置した。次いでを２０００回転／分で１
５分間遠心し、白濁固形物質を分離し、水（２０ｍＬ）
を加え、攪拌後、同様に遠心した。同じ洗浄操作を更に
２回繰り返した後、すぐ凍結乾燥した。得られた白色粉
末状物質（約０．１１ｇ）の透過型電子顕微鏡観察によ
れば、生じたマイクロカプセルの直径は、ややばらつく
ものの、２乃至５μｍである。Example 6 A keratin aqueous solution (keratin concentration: 1.4% by weight) obtained in Production Example 2 was placed in a wide-mouth test tube (10 m
L) and toluene (10 mL) were added, and the mixture was sonicated at 25 ° C. for 5 minutes in a nitrogen gas atmosphere. 30% aqueous hydrogen peroxide (0.07 mL) was added to the resulting white suspension, and the mixture was gently shaken and then left for 15 minutes. Then 1 at 2000 rpm
Centrifuge for 5 minutes to separate the cloudy solid material, and water (20 mL)
Was added, and the mixture was stirred and then centrifuged in the same manner. The same washing operation was repeated twice more, and then immediately freeze-dried. According to a transmission electron microscope observation of the obtained white powdery substance (about 0.11 g), the diameter of the generated microcapsules is 2 to 5 μm although it varies slightly.
【００６１】（実施例７）広口試験管にコラーゲン（タ
イプＩ）（０．５％、コーケン社製、I-PC）（１０ｍ
Ｌ）を入れ、２８％アンモニア水で弱アルカリにした。
ついで製造例２で得たケラチン水溶液（ケラチン濃度
１．４重量％）（６ｍＬ）を加え、５０℃にて１０乃至
１５分間振盪した。当初ゲル化した混合物が流動液とな
った後、トルエン（１０ｍＬ）を入れ、マグネットバー
で混合物を間接的に攪拌しつつ、２５℃にて３５Ｗの出
力で３分間、超音波照射した。生じた白色懸濁液を２０
００回転／分で１５分間遠心し、白色固形物を分離し、
水（２０ｍＬ）を加え、攪拌後、更に遠心した。同じ洗
浄操作を更に２回繰り返した後、白色懸濁液を凍結乾燥
した。得られた白色粉末状物質（約０．１０ｇ）は透過
型電子顕微鏡観察によれば、比較的均一なマイクロカプ
セルであり、壁厚は約０．０２μｍ、直径１．５乃至３
μｍである。この白色粉末状物質の光散乱測定もほぼ同
様の直径分布を示した。Example 7 Collagen (Type I) (0.5%, Koken Co., I-PC) (10 m) was placed in a wide-mouth test tube.
L) was added and made weak alkaline with 28% ammonia water.
Then, the keratin aqueous solution (keratin concentration 1.4% by weight) (6 mL) obtained in Production Example 2 was added, and the mixture was shaken at 50 ° C. for 10 to 15 minutes. After the initially gelled mixture became a fluid, toluene (10 mL) was added, and the mixture was ultrasonically irradiated at 25 ° C. and 35 W for 3 minutes while indirectly stirring the mixture. The resulting white suspension is 20
Centrifuge at 00 rpm for 15 minutes to separate the white solid,
Water (20 mL) was added, and the mixture was stirred and then centrifuged. After repeating the same washing operation twice more, the white suspension was freeze-dried. The obtained white powdery substance (about 0.10 g) is a comparatively uniform microcapsule according to the observation by a transmission electron microscope, the wall thickness is about 0.02 μm, and the diameter is 1.5 to 3.
μm. The light scattering measurement of this white powdery substance showed almost the same diameter distribution.
【００６２】（実施例８）広口試験管にメルカプト基を
担持したポリビニルアルコール（分子量２０００、ＳＨ
基１乃至３個）の２．５％水溶液（３ｍＬ）をいれ、次
いで製造例２で得たケラチン水溶液（ケラチン濃度１．
４重量％）（２０ｍＬ）を加え、充分に振動攪拌した。
次いでシリコン油（ALDRICH 社) を２重量％溶解した１
−フルオロシクロヘキサン（１０ｍＬ）を入れ、マグネ
ットバーで混合物を間接的に攪拌しつつ、２５℃にて５
０Ｗの出力で３分間、超音波処理した。生じた白色懸濁
液を２０００回／分で１５分間遠心し、白濁固形物を分
離し、純水（５ｍＬ）に分散保存した。同分散液を凍結
乾燥すると、約０．２８ｇの粉末が得られた。分散液
は、電子顕微鏡観察によれば、比較的均一な粒子を含
み、光散乱測定によれば、２乃至８μｍの主たる直径分
布を示した。上記遠心処理で分離した有機溶媒層が約１
乃至２ｍＬと少ない上、その濃縮により得られた残渣の
シリコン量が使用量の５乃至２０％であることから、シ
リコンがマイクロカプセルに含包されていることは明ら
かである。Example 8 Polyvinyl alcohol carrying a mercapto group in a wide-mouth test tube (molecular weight 2000, SH
2.5% aqueous solution (3 mL) of 1 to 3 groups was added, and then the keratin aqueous solution obtained in Production Example 2 (keratin concentration 1.
4% by weight) (20 mL) was added, and the mixture was sufficiently shaken and stirred.
Then, 2% by weight of silicon oil (ALDRICH) was dissolved 1
-Add fluorocyclohexane (10 mL) and stir the mixture indirectly with a magnet bar at 5 ° C at 5 ° C.
Sonicate for 3 minutes at 0 W power. The resulting white suspension was centrifuged at 2000 times / min for 15 minutes to separate a cloudy solid matter, which was dispersed and stored in pure water (5 mL). The dispersion was freeze-dried to obtain about 0.28 g of powder. The dispersion liquid contained relatively uniform particles as observed by an electron microscope, and showed a main diameter distribution of 2 to 8 μm by light scattering measurement. The organic solvent layer separated by the above centrifugal treatment is about 1
Since it is as small as 2 mL and the amount of silicon in the residue obtained by the concentration is 5 to 20% of the used amount, it is clear that the silicon is contained in the microcapsules.
【００６３】（実施例９）実施例４のトルエンの代わり
にビタミンＫの３重量％トルエン溶液（１０ｍＬ）を用
いる他は、全く同じ操作でマイクロカプセルを得た
（０．３０ｇ）。マイクロカプセルのエタノール分散液
の紫外吸収スペクトル測定より、使用したビタミンＫの
７０％がマイクロカプセルに含包されていることが明ら
かとなった。Example 9 Microcapsules (0.30 g) were obtained by exactly the same operation except that a 3 wt% toluene solution of vitamin K (10 mL) was used in place of toluene in Example 4. From the ultraviolet absorption spectrum measurement of the ethanol dispersion of the microcapsules, it was revealed that 70% of the used vitamin K was contained in the microcapsules.
【００６４】〔試験例１〕ケラチン膜からのケラチンの
剥離量： ガラス表面に、製造例２の方法で得たケラチン水溶液と
特公昭５９−３３０１７号記載の方法による水溶性ケラ
チン加水分解物（同濃度：平均分子量２２００）とを用
いて、それぞれケラチン薄膜（厚さ約１００μｍ）を調
製した。これをｐＨ７．４のトリス塩酸緩衝液に浸し、
４０℃にて振盪した。水溶液を一定量採取し、溶解した
タンパク質量をLowry 法で定量し、剥離量を産出した。
結果を表１に示す。Test Example 1 Amount of Keratin Removed from Keratin Film: On the glass surface, the keratin aqueous solution obtained by the method of Production Example 2 and the water-soluble keratin hydrolyzate by the method described in JP-B-59-33017 (the same as the above). Concentration: average molecular weight 2200) was used to prepare keratin thin films (thickness: about 100 μm), respectively. Soak this in Tris-HCl buffer of pH 7.4,
Shake at 40 ° C. A fixed amount of the aqueous solution was sampled, the amount of dissolved protein was quantified by the Lowry method, and the amount of exfoliation was produced.
The results are shown in Table 1.
【００６５】[0065]
【表１】 [Table 1]
【００６６】なお、特公昭５９−３３０１７号に記載の
方法による平均分子量１５０００の水溶性ケラチン加水
分解物を用いてケラチン薄膜の調製をも試みたが、製膜
化は困難であった。An attempt was also made to prepare a keratin thin film by using a water-soluble keratin hydrolyzate having an average molecular weight of 15,000 according to the method described in JP-B-59-33017, but film formation was difficult.
【００６７】[0067]
【発明の効果】以上の通り、本発明によれば、天然ケラ
チンを壁材とし、壁厚が薄くしかも安定性が高い極めて
微細且つ均一な粒径の高い含包量を有するマイクロカプ
セルを容易に製造することができる。また本発明のマイ
クロカプセルは、ケラチン加水分解物を壁材とする公知
技術のマイクロカプセルと比較して、マイクロカプセル
の製造効率、安定性等において格段に優れる。更に、本
発明のマイクロカプセルは、天然のケラチン鎖間の架橋
を一旦切離し、再びこれを形成してなる再生天然ケラチ
ンを壁材とするものであって、ケラチン鎖自身の切断等
の非可逆的化学修飾を伴わないものであるため、生体適
合性の点で好ましく、既述の通り多方面での利用が可能
である。Industrial Applicability As described above, according to the present invention, it is possible to facilitate the production of microcapsules having natural keratin as a wall material, a thin wall thickness and a high stability, an extremely fine and uniform particle size and a high encapsulation amount. It can be manufactured. Further, the microcapsules of the present invention are remarkably excellent in production efficiency, stability, etc. of microcapsules, as compared with known microcapsules having a keratin hydrolyzate as a wall material. Further, the microcapsule of the present invention uses as a wall material a regenerated natural keratin obtained by once separating the crosslinks between natural keratin chains and forming the crosslinks again, and is irreversible such as cutting of the keratin chain itself. Since it does not involve chemical modification, it is preferable in terms of biocompatibility and can be used in various fields as described above.
フロントページの続き (51)Int.Cl.5 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ｂ０１Ｊ 13/02 Ｃ０８Ｌ 89/04 ＬＳＥ 7415−4Ｊ Continuation of front page (51) Int.Cl. 5 Identification code Office reference number FI technical display location B01J 13/02 C08L 89/04 LSE 7415-4J
Claims (8)
プセル。1. Microcapsules containing regenerated natural keratin as a wall material.
を液体媒体中において還元剤で処理してケラチンを抽出
することにより得られる水溶性ケラチンを、マイクロカ
プセルの壁の形態に不溶化させてなるものである、請求
項１に記載のマイクロカプセル。2. The regenerated natural keratin obtained by insolubilizing water-soluble keratin obtained by treating a keratin-containing substance with a reducing agent in a liquid medium to extract keratin in the form of a wall of a microcapsule. The microcapsule according to claim 1, which is
物質を液体媒体中において還元剤で処理してケラチンを
抽出することにより得られる水溶性ケラチンと、メルカ
プト基若しくはジスルフィド結合を有するタンパク質若
しくはポリペプチド及び／又はメルカプト基若しくはジ
スルフィド結合を担持したポリビニルアルコールとの混
合物を、マイクロカプセルの壁の形態に不溶化させてな
るものであることを特徴とするマイクロカプセル。3. A water-soluble keratin obtained by treating a keratin-containing substance with a reducing agent in a liquid medium to extract keratin, and a protein or polypeptide having a mercapto group or a disulfide bond as a wall material of the microcapsule. And / or a mixture with a polyvinyl alcohol carrying a mercapto group or a disulfide bond, which is insolubilized in the form of the wall of the microcapsule.
元剤で処理してケラチンを抽出することにより得られる
水溶性ケラチンを、壁材原料として芯物質の周囲に被覆
させて不溶化させることよりなる、再生天然ケラチンを
壁材とするマイクロカプセルの製造方法。4. A water-soluble keratin obtained by treating a keratin-containing substance with a reducing agent in a liquid medium to extract keratin, which is coated with the periphery of a core substance as a wall material to insolubilize it. A method for producing microcapsules using recycled natural keratin as a wall material.
元剤で処理してケラチンを抽出することにより得られる
水溶性ケラチンと、メルカプト基若しくはジスルフィド
結合を有するタンパク質若しくはポリペプチド及び／又
はメルカプト基若しくはジスルフィド結合を担持したポ
リビニルアルコールとの混合物を、壁材原料として芯物
質の周囲に被覆させこれを不溶化させることよりなるマ
イクロカプセルの製造方法。5. A water-soluble keratin obtained by treating a keratin-containing substance with a reducing agent in a liquid medium to extract keratin, a protein or polypeptide having a mercapto group or a disulfide bond, and / or a mercapto group or a disulfide. A method for producing microcapsules, which comprises coating a mixture of polyvinyl alcohol carrying a bond with a core material as a wall material and insolubilizing the core material.
難溶性の液状物質である芯物質と混合し、これを超音波
処理及び／又は激しく攪拌することを特徴とする、請求
項４又は５に記載の製造方法。6. The method according to claim 4, wherein the aqueous solution containing the wall material is mixed with a core substance which is a liquid substance insoluble or hardly soluble in water, and the mixture is subjected to ultrasonic treatment and / or vigorous stirring. Or the manufacturing method according to 5.
る酸化剤を前記超音波処理及び／又は激しい攪拌の前に
添加し攪拌することを特徴とする、請求項６に記載の製
造方法。7. The method according to claim 6, wherein an oxidizing agent capable of converting a thiol group into a disulfide bond is added and stirred before the ultrasonic treatment and / or vigorous stirring.
能力を欠くガス雰囲気下にて行った後、チオール基をジ
スルフィド結合に変換し得る酸化剤を添加し攪拌するこ
とを特徴とする、請求項６に記載の製造方法。8. The ultrasonic treatment and / or vigorous stirring is performed in a gas atmosphere lacking an oxidizing ability, and then an oxidizing agent capable of converting a thiol group into a disulfide bond is added and stirred. The manufacturing method according to claim 6.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP04116819A JP3094181B2 (en) | 1992-04-09 | 1992-04-09 | Microcapsule using recycled natural keratin as wall material and method for producing the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP04116819A JP3094181B2 (en) | 1992-04-09 | 1992-04-09 | Microcapsule using recycled natural keratin as wall material and method for producing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH05285374A true JPH05285374A (en) | 1993-11-02 |
| JP3094181B2 JP3094181B2 (en) | 2000-10-03 |
Family
ID=14696420
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP04116819A Expired - Fee Related JP3094181B2 (en) | 1992-04-09 | 1992-04-09 | Microcapsule using recycled natural keratin as wall material and method for producing the same |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3094181B2 (en) |
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